Serum albumin oxidation and inter-alpha-trypsin-inhibitor heavy chain-4 abundance correlate with the dystropathology in the rat model of Duchenne muscular dystrophy
4 affiliations
- 1School of Molecular Sciences, University of Western Australia, Perth, WA, Australia
- 2Therassay Platform, Nantes Université, Nantes, France
- 3School of Human Sciences, University of Western Australia, Perth, WA, Australia
- 4TaRGeT Lab, Nantes Université, Nantes, France
Abstract
Duchenne muscular dystrophy (DMD) is a fatal X-linked genetic disease caused by the absence of functional dystrophin, resulting in muscle membrane fragility, chronic inflammation, and progressive muscle wasting. The lack of effective treatments is further compounded by the slow onset of measurable changes in clinical outcomes, such as muscle strength, which often take a year or longer to become evident. Blood-based biomarkers that can predict treatment efficacy and monitor disease progression would significantly accelerate therapeutic development. We propose that oxidative modifications to proteins in blood, a consequence of muscle inflammation, could be used to monitor disease progression in DMD. Using the DMDmdx rat, a model with more severe dystropathology than the mouse model of dystrophy (mdx), we assessed inflammation and oxidative stress in muscle and blood across disease stages. DMDmdx rats aged 1.5–12 months showed sustained immune activation, as indicated by elevated circulating leukocytes and increased myeloperoxidase content in dystrophic muscle compared with wild type. Oxidative protein modifications, including carbonylation, tyrosine chlorination, and thiol oxidation, were significantly elevated in serum and tissues of dystrophic rats. Two proteins showed distinct disease-associated oxidative changes: albumin, which exhibited consistently increased thiol oxidation across ages, and inter-alpha-trypsin inhibitor 4 (ITIH4), which showed elevated chlorination between 1.5 and 4.5 months. Notably, serum ITIH4 abundance correlated with markers of muscle inflammation and oxidative stress. These findings identify serum albumin thiol oxidation and serum ITIH4 abundance as promising blood-based biomarkers for monitoring inflammation-associated dystropathology in DMD.
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BibTeX
@article{bautista2026serum,
title = {{Serum albumin oxidation and inter-alpha-trypsin-inhibitor heavy chain-4 abundance correlate with the dystropathology in the rat model of Duchenne muscular dystrophy}},
author = {Angelo Patrick R. Bautista and Aude Lafoux and Irene Tsioutsias and Jessica R. Terrill and Caroline Le Guiner and Corinne Huchet and Peter G. Arthur},
journal = {Biochemical Journal},
year = {2026},
month = oct,
doi = {10.1042/bcj20260160},
url = {https://doi.org/10.1042/bcj20260160},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Serum albumin oxidation and inter-alpha-trypsin-inhibitor heavy chain-4 abundance correlate with the dystropathology in the rat model of Duchenne muscular dystrophy
AU - Angelo Patrick R. Bautista
AU - Aude Lafoux
AU - Irene Tsioutsias
AU - Jessica R. Terrill
AU - Caroline Le Guiner
AU - Corinne Huchet
AU - Peter G. Arthur
PY - 2026
DA - 2026/10/27
JO - Biochemical Journal
DO - 10.1042/bcj20260160
UR - https://doi.org/10.1042/bcj20260160
AB - Duchenne muscular dystrophy (DMD) is a fatal X-linked genetic disease caused by the absence of functional dystrophin, resulting in muscle membrane fragility, chronic inflammation, and progressive muscle wasting. The lack of effective treatments is further compounded by the slow onset of measurable changes in clinical outcomes, such as muscle strength, which often take a year or longer to become evident. Blood-based biomarkers that can predict treatment efficacy and monitor disease progression would significantly accelerate therapeutic development. We propose that oxidative modifications to proteins in blood, a consequence of muscle inflammation, could be used to monitor disease progression in DMD. Using the DMDmdx rat, a model with more severe dystropathology than the mouse model of dystrophy (mdx), we assessed inflammation and oxidative stress in muscle and blood across disease stages. DMDmdx rats aged 1.5–12 months showed sustained immune activation, as indicated by elevated circulating leukocytes and increased myeloperoxidase content in dystrophic muscle compared with wild type. Oxidative protein modifications, including carbonylation, tyrosine chlorination, and thiol oxidation, were significantly elevated in serum and tissues of dystrophic rats. Two proteins showed distinct disease-associated oxidative changes: albumin, which exhibited consistently increased thiol oxidation across ages, and inter-alpha-trypsin inhibitor 4 (ITIH4), which showed elevated chlorination between 1.5 and 4.5 months. Notably, serum ITIH4 abundance correlated with markers of muscle inflammation and oxidative stress. These findings identify serum albumin thiol oxidation and serum ITIH4 abundance as promising blood-based biomarkers for monitoring inflammation-associated dystropathology in DMD.
SN - 0264-6021
SN - 1470-8728
ER -